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Biomedical subjects

J S Richards

Publications and source records attributed to J S Richards.

At least 19 recordsLinked to original sources

Obesity intervention in persons with spinal cord injury.

STUDY DESIGN: A single group uncontrolled trial. OBJECTIVES: Despite widespread emphasis on the obesity-related health risks in persons with spinal cord injury (SCI), limited research has been carried out to intervene in this problem. This study was conducted to assess the initial effectiveness of a weight loss program on various health outcomes in persons with SCI. SETTING: A rehabilitation center in Birmingham, Alabama, United States. METHODS: A total of 16 individuals with chronic SCI who were overweight or obese participated in a weight management program that consisted of 12 weekly classes, covering nutrition, exercise, and behavior modification. Various outcomes were examined over a 6-month period (baseline, week 12, and week 24), including body composition measured by dual energy X-ray absorptiometry, physiologic measures, diet behavior, and psychosocial and physical functioning. Of these, 13 participants returned for the week 24 follow-up. RESULTS: Weight loss averaged 3.5+/-3.1 kg (3.8% of the initial weight) at week 12 and 2.9+/-3.7 kg (3.0% of the initial weight) at week 24. There was a significant reduction from baseline values at weeks 12 and 24 in body mass index, anthropometric measurements, and fat mass and improvement in diet behavior and psychosocial and physical functioning, while lean mass and blood albumin and hemoglobin levels were maintained. A correlation analysis showed that a greater weight loss was importantly (r>0.4) associated with a greater reduction in total cholesterol at weeks 12 and 24 and in systolic and diastolic blood pressure at week 24. Several factors were important (r>0.4 or r<-0.4) in determining the success in weight loss, including age, race, marital and employment status, family history of overweight/obesity, level and duration of injury, and cholesterol level at baseline. CONCLUSIONS: This is the first demonstration that a carefully planned program with time-calorie displacement diet is effective for overweight/obese individuals with SCI to lose weight without compromising total lean mass and overall health. It provides foundation for a future large clinical trial for weight loss of persons with SCI or other spinal cord dysfunction.

Adult↗

Test-retest reliability of the Donovan spinal cord injury pain classification scheme.

STUDY DESIGN: Videotape rating by independent viewers. OBJECTIVE: To determine the test-retest reliability of the Donovan spinal cord injury (SCI) pain classification scheme. SETTING: Rehabilitation Centre, Alabama, USA. METHODS: A total of 28 individuals with SCI reported 60 pain sites. A structured interview and physical exam were used to illicit information to classify each pain site according to the Donovan criteria. All structured interviews and exams were videotaped. Three independent raters viewed the videotapes on two occasions, separated by a 3-month interval, and classified each pain site using the Donovan pain classification scheme. RESULTS: Considering all three raters together, 78% of the pain sites were consistently classified from one period to the next. Within each rater, consistent classification ranged from 67 to 83%. However, inter-rater agreement for the classification of each pain site into the various types of pain was low for both periods (about 50-60%). CONCLUSIONS: Pain classification within each rater generally showed adequate test-retest reliability when using the Donovan SCI pain classification scheme. However, reliability estimates of agreement across raters highlight the ongoing need to exam and improve the psychometric characteristics of the various pain classification schemes.

Adult↗

Regulation of transcripts encoding ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin-like motifs-1) and progesterone receptor by human chorionic gonadotropin in equine preovulatory follicles.

One member of a new family of metalloproteinases, a disintegrin and metalloproteinase with thrombospondin-like motifs-1 (ADAMTS-1), has been found to be expressed and hormonally induced in granulosa cells of ovulating rodent follicles. Furthermore, the targeted disruption of the ADAMTS-1 gene resulted in ovarian defects associated with severely impaired fertility. While these data demonstrate the importance of ADAMTS-1 in rodent ovarian physiology, the potential role of ADAMTS-1 in the ovulatory process of monoovulatory species remains unknown. The objectives of this study were to clone the equine ADAMTS-1 primary transcript and to study its regulation during human chorionic gonadotropin (hCG)-induced ovulation. A 3573 bp follicular cDNA library clone was isolated and found to encode a nearly complete, highly conserved ADAMTS-1 homologue. Real-time RT-PCR analysis detected this transcript in diverse tIssues, including previously unreported sites of ADAMTS-1 expression such as the male reproductive tract, the follicular theca interna and the mature corpus luteum. The tIssue distribution of the progesterone receptor (PR), a known regulator of ADAMTS-1 expression in rodent preovulatory follicles, was found to overlap that of ADAMTS-1 in some tIssues. A study of the regulation of follicular ADAMTS-1 and PR mRNAs during the hCG-induced ovulatory process revealed distinct patterns of regulation in granulosa cells and in theca interna. In granulosa cells, ADAMTS-1 mRNA was found to be induced at 12 h post-hCG (P<0.05), followed by a return to basal levels by 30 h and a re-increase at 33-39 h (P<0.05). A concomitant increase in PR mRNA (P<0.05) was observed at 12 h post-hCG. In theca interna, abundant ADAMTS-1 mRNA was detected at all timepoints, and levels increased transiently at 33 h post-hCG (P<0.05), whereas no significant change was observed in PR mRNA. Together, these data demonstrate for the first time the hormonally regulated ovarian expression of ADAMTS-1 in a monoovulatory species, and identify a novel biphasic regulation of ADAMTS-1 in granulosa cells and a regulated expression in theca interna that were not previously observed in rodents.

ADAM Proteins↗

Metallothionein-1 messenger RNA transcription in steroid-secreting cells of the rat ovary during the periovulatory period.

An increase in metallothionein 1 (MT-1) mRNA was detected in the ovaries of immature Wistar rats that were primed with s.c. injection of 10 IU eCG followed 48 h later by 10 IU hCG s.c. to initiate the ovulatory process. Ovarian RNA was extracted at 0, 2, 4, 8, 12, 24, 72, 144, and 288 h after the primed animals were injected with hCG. These extracts were used for reverse transcription polymerase chain reaction (RT-PCR) differential display and Northern analyses that yielded complementary gene fragments for MT-1. Expression of MT-1 mRNA increased significantly by 24 h after hCG treatment and reached a peak at 144 h after hCG. In contrast, a disintegrin and metalloproteinase with thrombospondin motifs and a tissue inhibitor of metalloproteinase 1, which were also detected by the RT-PCR differential display procedure, reached a peak at 12 h after hCG and returned to control levels in the ovaries by 72 h after hCG. In situ hybridization indicated that most of the MT-1 mRNA was expressed in the vicinity of the theca interna of preovulatory follicles and in the lutein granulosa of postovulatory follicles. Thus, MT-1 mRNA expression is primarily in the vicinity of steroid-secreting areas of the ovary. The substantial increase in MT-1 mRNA expression might be important in protecting the ovarian tissues from oxidative stress generated by ovarian inflammatory events during the ovulatory process and luteinization.

ADAM Proteins↗

Delivery of the oocyte from the follicle to the oviduct: a time of vulnerability.

The multiplicity of genes regulated by the actions of LH in specific granulosa cell and cumulus cell microenvironments of the follicle during ovulation has now revealed how complex and finely tuned the ovulation process is. Although many proteases are expressed in the ovary and are hormonally regulated, the novel proteases ADAMTS-1 and cathepsin L, rather than the MMPs, have gained particular recognition. These may play critical roles in the eventual rupture of the follicle at the ovarian surface. Rupture is only one part of ovulation. Another important aspect is the actual release of the oocyte from the ovulation pore. Several recent studies have shown that the production of the matrix that is evidenced by cumulus expansion is somehow critical for extrusion to occur and for the oocyte to travel into the oviduct. At any point the oocyte may be trapped within a non-ovulating structure. Lastly, if the events of ovulation fail to occur before the events of luteinization are complete, oocytes are destined to degenerate within the non-ovulating structures.

ADAM Proteins↗

Pain classification following spinal cord injury: the utility of verbal descriptors.

OBJECTIVES: To determine the predictive utility of verbal descriptors to distinguish between pain types following spinal cord injury (SCI). DESIGN: Cross-sectional. SETTING: USA. METHODS: Participants (n=29) completed the Short Form - McGill Pain Questionnaire (SF-MPQ) for each pain site reported. A total of 64 pain sites were reported with 80% of the sample reporting multiple pain sites. Each pain site was categorized using three different SCI pain classification schemes. The predictive utility of verbal descriptors to distinguish between pain types was examined statistically using (1) each word separately, (2) a combination of words (ie, the SF-MPQ total subscales, the number of words chosen on each scale), and (3) discriminant function analysis. RESULTS: There was a substantial overlap in the use of verbal descriptors across pain types. Few differences across pain types were found for endorsement of individual words, and differences across pain types were not found for any of the word combination scores. The majority of the verbal descriptors did not enter the step-wise discriminant functions for each SCI pain classification scheme, however, 'tingling' and 'aching' showed modest predictive utility for neuropathic and musculoskeletal pain, respectively. Correct classification was in the low range (ie, 39% to 82%, average=60%, with a 33% chance level). All three pain classification schemes showed the same general pattern of results. CONCLUSION: In general, verbal descriptors alone offered marginal utility with regard to identifying specific pain types following SCI. Future directions alone and implications are discussed.

Adult↗

Gonadotropin-induced expression of pancreatitis-associated protein-III mRNA in the rat ovary at the time of ovulation.

The ovulatory process in mammals involves gross physiological events in the ovary that cause transient deterioration of the ovarian connective tissue and rupture of the apical walls of mature follicles. This gonadotropin-induced process has features similar to an acute inflammatory reaction that affects most of the ovary. The present study reveals that the ovulatory events include induction of mRNA for pancreatitis-associated protein-III (PAP-III). Immature Wistar rats were primed with 10 IU equine chorionic gonadotropin s.c., and 48 h later the 12-h ovulatory process was initiated by 10 IU human chorionic gonadotropin (hCG) s.c. Ovarian RNA was extracted at 0, 2, 4, 8, 12 and 24 h after the animals were injected with hCG. The RNA extracts were used for RT-PCR differential display to detect PAP-III gene expression in the stimulated ovarian tissue. Northern blotting showed that transcription was significantly greater at 4-12 h after the ovaries had been stimulated by hCG. In situ hybridization indicated that PAP-III mRNA expression was limited mainly to the hilar region of the ovarian stroma, with most of the signal emanating from endothelial cells that lined the inner walls of blood vessels, and from small secondary follicles. Treatment of the animals with ovulation-blocking doses of indomethacin (an inhibitor of prostanoid synthesis) or epostane (an inhibitor of progesterone synthesis) revealed that ovarian transcription of PAP-III mRNA was moderately dependent on ovarian progesterone synthesis. In conclusion, the present evidence of an increase in PAP-III gene expression in gonadotropin-stimulated ovaries provides further evidence that the ovulatory process is comparable to an inflammatory reaction.

Androstenols↗

Quality of life after spinal cord injury caused by gunshot.

OBJECTIVE: To determine what effect gunshot-caused spinal cord injury (SCI) has on self-reported quality of life (QOL) and on the frequency of pain sufficient to interfere with day-to-day activities. DESIGN: Follow-up, case-control design. SETTING: Analysis of data obtained from the (US) National Spinal Cord Injury Statistical Center from 18 funded Spinal Cord Injury Model Systems. PARTICIPANTS: Individuals with traumatic onset SCI (n = 1901). From these, 111 persons with gunshot-caused SCI were matched to persons with nongunshot SCI. MAIN OUTCOME MEASURES: Satisfaction with Life Scale (SWLS), the Craig Handicap Assessment and Reporting Technique (CHART), Medical Outcomes Study Short-Form Health Survey (SF-12), and an individual pain item from the SF-12. RESULTS: No between-group differences were found on any of the QOL outcome measures. In contrast, those with SCI caused by gunshot reported that pain more frequently interfered with day-to-day activities than the matched comparison group. CONCLUSIONS: SCI caused by gunshot appears largely unrelated to QOL, after controlling for demographic and medical characteristics associated with this group. Gunshot as a mechanism of SCI may place individuals at an increased risk of subsequent development of pain that interferes with activities of daily living.

Adult↗

Predictors of pain 1 year post-spinal cord injury.

OBJECTIVE: To determine the predictive validity of demographic and medical characteristics to the subsequent development of pain 1 year post-spinal cord injury (SCI). DESIGN: Prospective longitudinal design using data from 18 Model Spinal Cord Injury Systems of Care. PARTICIPANTS: Adults 18 years or older with traumatic-onset SCI (n = 540) evaluated at 1 year postinjury. OUTCOME MEASURES: A single item from the Short Form-12 that assessed pain interference in day-to-day activities using a 5-point Likert scale. PREDICTOR VARIABLES: Demographic and medical characteristics, individual and total medical complications during rehabilitation, and insurance provider. RESULTS: Univariate analyses showed age, education, marital status, primary occupation at the time of injury, American Spinal Injury Association motor score, and sponsor of care to be related to pain interference 1 year post-SCI. Polychotomous logistic regression indicated that age and occupational status at the time of injury were the only significant unique predictors of pain interference. The youngest (aged 18-29 years) and oldest (aged 60 years and older) age groups reported the least amount of pain interference, whereas individuals unemployed at the time of injury were significantly more likely to report pain interference. None of the other predictor variables was significant. CONCLUSION: Age and occupational status appear to be important predictors of pain interference 1 year post-SCI. Future directions of study and limitations are discussed.

Adult↗

Impact of demographic and medical factors on satisfaction with life after spinal cord injury: a normative study.

OBJECTIVE: The aim of this study was (1) to examine demographic and medical predictors of the Satisfaction With Life Scale (SWLS) among individuals with spinal cord injury (SCI) and (2) to provide a normative table for the SWLS that includes appropriate adjustments for the most important predictors of life satisfaction. STUDY DESIGN: We examined predictors of the SWLS including age, education, sex, race, injury duration, number of rehospitalizations, marital status, employment status, SCI etiology, and level of neurological impairment. PARTICIPANTS: Individuals in the National Spinal Cord Injury Statistical Center database [from 18 SCI model systems (1995-1999)] undergoing follow-up assessment were included for study. OUTCOME MEASURE: Satisfaction With Life Scale. RESULTS: Univariate analyses indicated that marital and employment status, race, sex, education, and injury duration were significant factors associated with scores on the SWLS. In general, individuals who were female, white, married, and currently employed and had a higher education and longer injury duration reported significantly higher scores on the SWLS (P < .01). Effect-size estimates for these factors ranged from 0.16 to 0.41. Regression analyses showed that education, employment status, and injury duration were the strongest unique predictors of satisfaction with life but accounted for only 10% of the variance. CONCLUSION: The SWLS is a global measure of life satisfaction and is relatively unrelated to demographic and medical characteristics. Normative tables are provided for epidemiologic comparison.

Adolescent↗

3alpha-hydroxysteroid dehydrogenase messenger RNA transcription in the immature rat ovary in response to an ovulatory dose of gonadotropin.

The ovulatory process in mammals involves a substantial increase in the metabolism of steroids and eicosanoids in response to a surge in LH or to an injection of hCG into experimental animals. This study provides evidence that the ovulatory stimulus causes induction of the gene for 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD), an enzyme that belongs to several oxidoreductase superfamilies that affect steroid and eicosanoid metabolism. Immature Wistar rats were primed with 10 IU eCG s.c., and 48 h later the 12-h ovulatory process was initiated by 10 IU hCG s.c. Ovarian RNA was extracted at 0, 2, 4, 8, 12, and 24 h after injecting the animals with hCG. The RNA extracts were used for reverse transcription-polymerase chain reaction (PCR) differential display to detect gene expression in the stimulated ovarian tissue. One of the PCR primer sets differentially amplified a cDNA fragment that is 52.3% homologous with a 3alpha-HSD gene in rat liver. Northern analyses revealed that maximum transcription was at 8 h after the animals had been treated with hCG. The Northerns also indicated that the 3alpha-HSD cDNA probe cross-hybridized with as many as six different bands of mRNA on the blots. In situ hybridization localized 3alpha-HSD mRNA in the granulosa and thecal layers of mature follicles and in newly formed corpora lutea at 24 h after the ovulatory stimulus. In conclusion, gene(s) for 3alpha-HSD are transcribed in ovarian follicles in response to an ovulatory dose of gonadotropin. A possible function of the oxidoreductase enzyme that is translated from the 3alpha-HSD mRNA may be to reduce the toxic aldehyde and ketone components of the steroids and eicosanoids that accumulate in the mammalian ovary at the time of ovulation.

3-Hydroxysteroid Dehydrogenases↗

Gunshot versus nongunshot spinal cord injury: acute care and rehabilitation outcomes.

OBJECTIVE: To examine the impact of gunshot-caused spinal cord injury on acute and rehabilitative care outcome using a case control design. DESIGN: Two groups (i.e., gunshot- vs. nongunshot-caused spinal cord injury) of 212 individuals were matched case-for-case on age (i.e., within 10 yr), education, gender, race, marital status, primary occupation, impairment level, and Model System region. Outcome measures included length of hospital stay, functional status (FIM), treatment charges, and home discharge rates. RESULTS: The two groups did not differ in the length of stay during acute and rehabilitative care, charges during rehabilitative care, or postrehabilitation discharge placement. Several significant between-group differences in treatment procedures were noted (e.g., prevalence of spinal surgery), which may, in part, account for the higher acute-care charges among those persons with nongunshot-caused spinal cord injury. CONCLUSION: Once an individual is stabilized and admitted for rehabilitative care, gunshot etiology of spinal cord injury seems largely unrelated to the initial rehabilitation outcome.

Adult↗

Nursing home residence: quality of life among individuals with spinal cord injury.

OBJECTIVE: To examine the quality of life among individuals with spinal cord injury currently living in a nursing home vs. community residence. DESIGN: A case-control design matched nursing home and community residents on numerous demographic and medical characteristics. Two groups of 37 individuals (nursing home vs. community residents) were matched case-for-case on age (i.e., within 10 yr), education, gender, race, marital status, and impairment level. Etiology of spinal cord injury, American Spinal Injury Association Impairment Index at the time of rehabilitation discharge, and injury duration, although not specifically matched, were not significantly different between groups (P > 0.05). Outcome measures included the Satisfaction With Life Scale, and the Craig Handicap Assessment and Reporting Technique (CHART). RESULTS: Results indicated that overall self-reported quality of life was significantly lower among nursing home residents compared with matched community-dwelling residents (mean = 18 and 14, respectively). Similarly, self-reported handicap was significantly higher among the nursing home residents compared with community residents (mean = 337 and 181, respectively), particularly in the areas of physical independence, mobility, occupational functioning, and economic self-sufficiency (P < 0.05). In contrast, the score on the CHART social integration subscale was similar across groups (P > 0.05). CONCLUSION: Despite matching numerous variables, the nursing home residents demonstrated significantly lower quality of life across multiple domains as compared with their community-dwelling counterparts. Additional research is needed to examine the specific mechanisms associated with these differences.

Adult↗

Bladder management and quality of life after spinal cord injury.

OBJECTIVE: This study examines the quality of life among individuals with spinal cord injury requiring assistance for bowel and bladder management vs. those with independent control of bowel and bladder. DESIGN: Two groups of 53 individuals each were matched case for case on age, education, sex, race, and lesion level. Outcome measures included the Satisfaction With Life Scale, the Craig Handicap Assessment and Reporting Technique (CHART), and the SF-12. RESULTS: Satisfaction with life was significantly lower among dependent individuals with impaired bowel and bladder functioning as compared with individuals with independent bowel and bladder control. Similarly, dependent individuals reported greater self-reported handicap (CHART) than independent individuals in the areas of physical independence, mobility, and occupational functioning. However, dependent and independent individuals did not differ in the areas of social integration and economic self-sufficiency. Item analysis on the CHART item assessing number of social contacts initiated in the previous month suggested that dependent individuals may have difficulty initiating new social contacts. Independent individuals reported better overall physical health (SF-12) than dependent individuals. Mental health (SF-12), however, did not differ across groups. CONCLUSIONS: Individuals with impaired bowel and bladder control reported lower quality of life on several domains compared with those with independent control of bowel and bladder. Though the two groups did not differ in self-reported social integration, dependent individuals may have greater difficulty creating new social relationships.

Adult↗

New signaling pathways for hormones and cyclic adenosine 3',5'-monophosphate action in endocrine cells.

The glycoprotein hormones, ACTH, TSH, FSH, and LH regulate diverse functions in endocrine cells. Although cAMP and PKA have long been shown to mediate specific intracellular signaling events including the transcription of specific genes via the CREB-CBP complex, recent observations have indicated that PKA does not account for all of the intracellular targets of cAMP. For example, TSH stimulation of thyroid cell proliferation is not completely blocked by PKA inhibitors. TSH and FSH can stimulate PKB phosphorylation by a PKAindependent but PI3-K/PDK1-dependent pathway. An FSH inducible kinase, Sgk, has recently been shown to be a close relative of PKB. Sgk is also a target of PI3-K-PDK1 pathway, indicating that some effects previously ascribed to PKB may be mediated by this inducible kinase. The identification of novel cAMP-binding proteins that exhibit guanine nucleotide exchange (GEF) activity (cAMP-GEFS; Epacs) has open new doors for cAMP action that include activation of small GTPases such as Rap1a, Rap2, and possibly Ras. These GTPases are known activators of downstream kinase cascades, including p38MAPK and Erk1/2 as well as PI3-K. Thus, FSH and TSH activation of PKB and Sgk may occur via this alternative cAMP pathway that involves cAMP-GEFs and the activation of the PI3-K/PDK1 pathway.

Adrenal Glands↗

Regulation of AP1 (Jun/Fos) factor expression and activation in ovarian granulosa cells. Relation of JunD and Fra2 to terminal differentiation.

AP1 transcription factors control rapid responses of mammalian cells to stimuli that impact proliferation, differentiation, and transformation. To determine which AP1 factors are present in and regulated by hormones in ovarian cells during specific stages of proliferation and differentiation, we used both in vitro and in vivo models, Western blotting, immunohistochemistry, DNA binding assays, and transfections of AP1 promoter-reporter constructs. The expression patterns of Jun and Fos family members in response to hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cAMP) were distinct. JunB, c-Jun, c-Fos, and Fra2 were rapidly but transiently induced by FSH in immature granulosa cells. JunD and Fra2 were induced by LH and maintained as granulosa cells terminally differentiated into luteal cells. Forskolin and phorbol myristate acetate acted synergistically to enhance transcription of an AP1(-73COL)-luciferase construct. JunD appears to be one mediator of this effect, since JunD was a major component of the AP1-DNA binding complex in granulosa cells, and menin, a selective inhibitor of JunD, blocked transcription of -73COL-luciferase. Thus, FSH and LH via cAMP induce specific AP1 factors, the AP1 expression patterns are distinct, and that of JunD and Fra2 correlates with the transition of proliferating granulosa cells to terminally differentiated, non-dividing luteal cells.

Animals↗

Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases.

Ovulation is a precisely timed process by which a mature oocyte is released from an ovarian follicle. This process is initiated by the pituitary surge of luteinizing hormone (LH), is temporally associated with transcriptional regulation of numerous genes, and is presumed to involve the synthesis and/or activation of specific proteases that degrade the follicle wall. The progesterone receptor (PR), a nuclear receptor transcription factor, is induced in granulosa cells of preovulatory follicles in response to the LH surge and has been shown to be essential for ovulation, because mice lacking PR fail to ovulate and are infertile. Using these mice as a model in which to elucidate PR-regulated genes in the ovulation process, we show that the matrix metalloproteinases MMP-2 and MMP-9 are not targets of PR during ovulation. In contrast, two other proteases, ADAMTS-1 (A disintegrin and metalloproteinase with thrombospondin-like motifs) and cathepsin L (a lysosomal cysteine protease), are transcriptional targets of PR action. ADAMTS-1 is induced after LH stimulation in granulosa cells of preovulatory follicles and depends on PR. Cathepsin L is induced in granulosa cells of growing follicles by follicle-stimulating hormone, but the highest levels of cathepsin L mRNA occur in preovulatory follicles in response to LH in a PR-dependent manner. The identification of two regulated proteases in the ovary, together with their abnormal expression in anovulatory PR knockout mice, suggests that each plays a critical role in follicular rupture and represents a major advance in our understanding of the proteolytic events that control ovulation.

ADAM Proteins↗